Hanna J, Waterman D, Isasa M, Elsasser S, Shi Y, Gygi S, Finley D.
J Biol Chem. 2014 Jan 17;289(3):1876-85. doi: 10.1074/jbc.M113.534032. Epub 2013 Dec 2.
Protein misfolding is a universal threat to cells. The ubiquitin-proteasome system mediates a cellular stress response capable of eliminating misfolded proteins. Here we identify Cuz1/Ynl155w as a component of the ubiquitin system, capable of interacting with both the proteasome and Cdc48. Cuz1/Ynl155w is regulated by the transcription factor Rpn4, and is required for cells to survive exposure to the trivalent metalloids arsenic and antimony. A related protein, Yor052c, shows similar phenotypes, suggesting a multicomponent stress response pathway. Cuz1/Ynl155w functions as a zinc-dependent ubiquitin-binding protein. Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome for destruction.
http://www.jbc.org/content/289/3/1876.long
Brigham and Women's Hospital, Harvard Medical School
United States
